title: Modulation with cytokines of radiation injury: suggested mechanisms of action.
abstract: Cytokines, hormonelike proteins, produced by stimulated cells and tissues, were found to protect mice against lethal hematopoietic failure caused by ionizing radiation. Radioprotection was achieved by pretreatment with interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-12, or stem cell factor (SCF) at 18 to 24 hr before irradiation. Pretreatment with antibodies to these cytokines rendered the mice more susceptible to radiation lethality, indicating that these cytokines play a role in innate resistance to radiation. In contrast, treatment with tumor growth factor beta (TGF-beta), a cytokine that inhibits cycling of primitive hematopoietic progenitors, sensitized mice to radiation lethality. The schedule of IL-1 administration was critical to its radioprotective effect. Evidence was obtained that this may be based on the induction of additional cytokines by IL-1. The radioprotective effects of cytokines can be based on induction of cycling of primitive progenitor cells (IL-1, SCF), prevention of apoptosis (SCF), and induction of scavenging proteins and enzymes (IL-1, TNF) that reduce oxidative damage. In contrast, radiosensitizing effects may be due to inhibition of progenitor cycling (TGF-beta) or enhanced progenitor cell apoptosis (TGF-beta). Thus, the insights gained from such studies at the whole-animal level promise a better understanding of the membrane and intracellular events associated with radiation damage and repair of such damage.
authors.affiliation: Office of International Health Programs, U.S. Department of Energy, Germantown, MD 20874, USA. ruth.neta@eh.doe.gov
authors.forename: R
authors.initials: R
authors.lastname: Neta
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000502:physiology / Q000627:therapeutic use*; D004064:Digestive System / Q000187:drug effects / Q000528:radiation effects; D007378:Interleukins / Q000627:therapeutic use; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D019089:Stem Cell Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D007378:Interleukins; D011837:Radiation-Protective Agents; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha